Several lines of transgenic mice have been produced which carry a functional HIV-1 envelope gene construct. These lines display a kidney pathology characterized by focal, segmented glomerulosclerosis and proteinuria resulting in premature death. These mice provide an animal model for HIV-associated renal pathology which has been well documented in humans infected with HIV-1. In order to develop alternative diagnostic and therapeutic approaches for the treatment of HIV, human monoclonal antibodies to the HIV gp-160 antigen have been produced in this laboratory. One specific human hybridoma which produces an IgG3 antibody specific for gp-160 and whose epitope corresponds to the gp-41 antigen has been newly characterized. It binds to the surface of HIV-infected cells, does not neutralize HIV virus, and binds in a specific manner to an epitope distinct from the gp-41 cross-reactive epitope on MHC class II antigens. Further studies on this and other monoclonal antibodies are being pursued. Ongoing work involving autoimmune responses in mice transgenic for herpes virus glycoprotein D have indicated the presence of message specific for gD as early as day 8 of gestation in mice negative for anti-gd antibodies upon challenge with recombinant vaccinia gD and partially tolerant to challenge with HSV. The onset and cell type specific expression of gD during development is currently being studied in situ. We have initiated the development of transgenic mice which carry the gene for the human complement component C3d (the EBV receptor in human 8 lymphocytes). Three founder mice have been established which carry a single copy of the transgene. These mice will be bred and subsequently infected with EBV in order to obtain a murine model in which to study EBV-mediated transformation in lymphoid cells.